title: Correlation between direct ELISA, single epitope-based inhibition ELISA and pseudovirion-based neutralization assay for measuring anti-HPV-16 and anti-HPV-18 antibody response after vaccination with the AS04-adjuvanted HPV-16/18 cervical cancer vaccine.
abstract: To monitor immune status during clinical trials and after vaccine registration, several assays have been developed to measure type-specific human papillomavirus (HPV) serum antibody levels. These include neutralization assays, single epitope-based inhibition immunoassays, and direct enzyme-linked immunosorbent assays (ELISAs). Neutralization assays based on multiple epitopes and independent of vaccine material are considered the 'gold standard' for unbiased assessment of the protective potential of vaccine-induced antibodies. However, their use in large clinical trials is challenging. Here, we compare both the direct ELISA and the single epitope-based inhibition ELISA with the pseudovirion-based neutralization assay (PBNA) for HPV-16/18 antibody responses in vaccinated women enrolled in trials of Cervarix, GSK's cervical cancer vaccine. The direct ELISA, which is based on multiple epitopes, was shown to have a higher degree of sensitivity and correlation with the PBNA when compared with the single epitope-based inhibition ELISA. Among double-positive results, high correlations were observed between the PBNA and the direct ELISA (0.70-0.88 for HPV-16 and 0.82-0.94 for HPV-18) and also with the single epitope-based inhibition ELISA (0.60-0.89 for HPV-16 and 0.57-0.96 for HPV-18) in women aged 15-25 years. The correlation persisted up to 6.4 years after primary vaccination. Similar levels of correlation were observed for adolescents aged 10-14 years and women aged 46-55 years. Therefore, the direct ELISA appears to be an excellent surrogate for neutralizing activity and can be used to evaluate antibody response induced by L1 virus-like particle-based cervical cancer vaccines, regardless of time elapsed after vaccination (up to 6.4 years) and the age of the vaccine recipient.
authors.affiliation: Research & Development, GlaxoSmithKline Biologicals, Rixensart, Belgium. francis.dessy@gskbio.com
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Dessy
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Giannini
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Bougelet
authors.forename: Troy J
authors.initials: TJ
authors.lastname: Kemp
authors.forename: Marie-Pierre M
authors.initials: MP
authors.lastname: David
authors.forename: Sylviane M
authors.initials: SM
authors.lastname: Poncelet
authors.forename: Ligia A
authors.initials: LA
authors.lastname: Pinto
authors.forename: Martine A
authors.initials: MA
authors.lastname: Wettendorff
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood*; D002648:Child; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D052162:Human papillomavirus 16 / Q000276:immunology*; D052161:Human papillomavirus 18 / Q000276:immunology*; D006801:Humans; D008875:Middle Aged; D009500:Neutralization Tests / Q000379:methods; D053918:Papillomavirus Vaccines / Q000276:immunology*; D012680:Sensitivity and Specificity; D013223:Statistics as Topic
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D053918:Papillomavirus Vaccines